Context: Children with familial hypercholesterolemia have endothelial d ysfunct ion and increased carotid intimamedia thickness(IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention thera py in the causal pathway of this disorder has been available for more than a dec ade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective: To determine the 2-year efficacy an d safety of pravastatin therapy in children with familial hypercholesterolemia. Design: Randomized, double-blind, placebo-controlled trial that recruited chil dren between December 7, 1997, and October 4, 1999, and followed them up for 2 y ears. Setting and Participants: Two hundred fourteen children with familial hype rcholesterolemia, aged 8 to 18 years and recruited from an academic medical refe rral center in the Netherlands. Intervention: After initiation of a fat-restric ted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n=106), or a plac ebo tablet (n=108). Main Outcome Measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 ye ars; the principal safety outcomes were growth, maturation, and hormone level me asurements over 2 years as well as changes in muscle and liver enzyme levels. Re sults: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean <>, -0.010 <<0.048>> mm; P=.049), whereas a trend toward pro gression was observed in the placebo group (mean <>, +0.005 <<0.044>> mm; P=.28 ). The mean (SD) change in IMT compared between the 2 groups (0.014 <<0.046>> mm) was significant (P=.02). Also, pravastatin significantly reduced mean low-densi ty lipoprotein cholesterol levels compared with placebo (-24.1%vs +0.3%, res pectively; P< .001). No differences were observed for growth, muscle or liver en zymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion: Two years of pravastatin th erapy induced a significant regression of carotid atherosclerosis in children wi th familial hypercholesterolemia, with no adverse effects on growth, sexual matu ration, hormone levels, or liver or muscle tissue. Context: Children with familial hypercholesterolemia have endothelial dsfunct ion and increased carotid intimamedia thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention thera py in the causal pathway of this disorder has been available for more than a Objective: To determine the 2-year efficacy an d safety of pravastatin therapy in children with familial hypercholesterolemia. Design: Randomized, double-blind , placebo-controlled trial that recruited chil dren between December 7, 1997, and October 4, 1999, and followed them up for 2 y ears. Setting and Participants: Two hundred fourteen children with familial hype rcholesterolemia, aged 8 to 18 years and recruited from an academic medical refe rral center in the Netherlands. Intervention: After initiation of a fat-restrictive diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg / d (n = 106), or a plac ebo tablet (n = 108). Main Outcome Measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 ye ars; the principal safety outcomes were growth, maturation, and hormone level me asurements over 2 years as well as changes in muscle and liver enzyme levels. Re sults: Compared with baseline, carotid IMT showed a trend toward pro regression with pravastatin (mean << SD >>, -0.010 << 0.048 >> mm; P = .049), while a trend toward pro gression was observed in the placebo group (mean << SD >>, The mean (SD) change in IMT compared between the two groups (0.014 << 0.046 >> mm) was significant (P = .02). Also, pravastatin reduced mean low-densi ty lipoprotein cholesterol levels compared with placebo (-24.1% vs + 0.3%, res pectively; P <.001). No differences were observed for growth, muscle or liver en zymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion: Two years of pravastatin th erapy induced a significant regression of carotid atherosclerosis in children wi th familial hypercholesterolemia, with no adverse effects on growth, sexual matu ration, hormone levels, or liver or muscle tissue.